Association of Sodium-Glucose Cotransporter 2 Inhibitor vs Dipeptidyl Peptidase-4 Inhibitor Use With Risk of Incident Obstructive Airway Disease and Exacerbation Events Among Patients With Type 2 Diabetes in Hong Kong

Importance Patients with diabetes are at higher risk for obstructive airway disease (OAD). In recent meta-analyses of post hoc analyses of cardiorenal trials, sodium-glucose cotransporter 2 inhibitors (SGLT2Is) were suggested to reduce the risk of OAD adverse events. However, a clinical investigation of this association is warranted. Objective This study aimed to investigate the association of SGLT2I use vs dipeptidyl peptidase-4 inhibitor (DPP4I) use with OAD incidence and exacerbation events in patients with type 2 diabetes. Design, Setting, and Participants This retrospective population-based cohort study used electronic health data from a territory-wide electronic medical database in Hong Kong. Data were collected for patients with type 2 diabetes who were prescribed SGLT2Is or DPP4Is between January 1, 2015, and December 31, 2018. Patients were followed for a median of 2.2 years between January 1, 2015, and December 31, 2020. A prevalent new-user design was adopted to match patients based on previous exposure to the study drugs. Propensity score matching was used to balance baseline characteristics. Exposures Patients with type 2 diabetes using SGLT2Is (exposure of interest) or DPP4Is (active comparator). Main Outcomes and Measures The main outcomes were the first incidence of OAD and the count of OAD exacerbations. The risk of incident OAD was estimated using a Cox proportional hazards regression model. The rate of exacerbations was estimated using zero-inflated Poisson regression. Statistical analysis was performed on November 13, 2022. Results This study included 30 385 patients. The propensity score–matched non-OAD cohort (incidence analysis) consisted of 5696 SGLT2I users and 22 784 DPP4I users, while the matched OAD cohort (exacerbations analysis) comprised 381 SGLT2I users and 1524 DPP4I users. At baseline, 56% of patients in the non-OAD cohort were men and the mean (SD) age was 61.2 (9.9) years; 51% of patients in the OAD cohort were men and the mean age was 62.2 (10.8) years. Compared with DPP4I use, SGLT2I use was associated with a lower risk of incident OAD (hazard ratio, 0.65 [95% CI, 0.54-0.79]; P < .001) and a lower rate of exacerbations (rate ratio, 0.54 [95% CI, 0.36-0.83]; P = .01). The associations were consistent in sex subgroup analysis. Conclusions and Relevance The findings of this retrospective cohort study of patients with type 2 diabetes in Hong Kong suggest that SGLT2I use was associated with a reduced risk of incident OAD and a lower rate of exacerbations in a clinical setting compared with DPP4I use. These findings further suggest that SGLT2Is may provide additional protective effects against OAD for patients with type 2 diabetes and that further investigation is warranted

Unveiling unique clinical phenotypes of hip fracture patients and the temporal association with cardiovascular events

Cardiovascular events are the leading cause of death among hip fracture patients. This study aims to identify subphenotypes of hip fracture patients and investigate their association with incident cardiovascular events, all-cause mortality, and health service utilisation in Hong Kong and the United Kingdom populations. By the latent class analysis, we show three distinct clusters in the Hong Kong cohort (n = 78,417): Cluster 1 has cerebrovascular and hypertensive diseases, hyperlipidemia, and diabetes; Cluster 2 has congestive heart failure; Cluster 3 consists of relatively healthy patients. Compared to Cluster 3, higher risks of major adverse cardiovascular events are observed in Cluster 1 (hazard ratio 1.97, 95% CI 1.83 to 2.12) and Cluster 2 (hazard ratio 4.06, 95% CI 3.78 to 4.35). Clusters 1 and 2 are also associated with a higher risk of mortality, more unplanned accident and emergency visits and longer hospital stays. Self-controlled case series analysis shows a significantly elevated risk of major adverse cardiovascular events within 60 days post-hip fracture. Similar associations are observed in the United Kingdom cohort (n = 27,948). Pre-existing heart failure is identified as a unique subphenotype associated with poor prognosis after hip fractures

Bone-targeting agents in major solid tumour metastases: a multinational cohort study

OBJECTIVE: To describe the epidemiology, clinical characteristics and utilisation patterns of bone-targeting agents (BTAs) in patients with bone metastases from breast, prostate and lung cancer. METHODS: This is a multinational retrospective cohort study including patients with three major solid tumours (breast, prostate and lung cancer) and newly initiated on BTAs (ie, denosumab, zoledronic acid and pamidronate). Records were retrieved from nationwide health databases from Hong Kong and Taiwan (HK and TW: 2013–2017) and Korea (KR: 2012–2016). Descriptive analyses included the annual incidence rates of bone metastases and the cumulative incidence curves of BTA initiation. We used Sankey diagrams to visualise the dynamic BTA utilisation patterns. RESULTS: The annual incidence rate of bone metastases ranged from 3.5% to 4.5% in TW, from 9.6% to 10.3% in HK and from 2.9% to 3.8% in KR. We identified 14.1% (5127), 9.3% (883) and 9.4% (4800) of patients with bone metastases newly initiated on BTAs in TW, HK and KR, respectively. The most frequently used BTA in TW (67.1%) and HK (51.9%) was denosumab, while in KR (84.8%) it was zoledronic acid. Sankey diagrams indicated the proportion of patients remaining on denosumab was highest in TW and HK, while it was zoledronic acid in KR. Specifically, in TW, patients who were on bisphosphonates or had discontinued treatment frequently switched to or reinitiated denosumab. CONCLUSIONS: We found the rate of BTA utilisation remained low across all sites and tumour types in recent years. The dynamic utilisation patterns of BTAs provide better understanding of the treatment landscape for future evaluation of associated outcomes of patients

Reply to: Association Between Alendronate and All-Cause Mortality and Cardiovascular Mortality Among Hip Fracture: An Alternative Explanation.

To the Editor: We are thankful to Prof. Nguyen and Dr. Tran for their interest in our study and we appreciate the opportunity to respond to their comments. As Prof. Nguyen and Dr. Tran suggested that censoring patients at the time of switching medications might have inflated the effect size, we investigated this potential bias by excluding patients with switching of medications. Of the 3,081 alendronate-treated patients, 281 patients (9.1%) switched the therapy during the study period. After excluding these patients, we observed similar findings (Table), suggesting that bias due to treatment of censoring data should be minimal in our study

Global epidemiology of hip fractures: a study protocol using a common analytical platform among multiple countries

INTRODUCTION: Hip fractures are associated with a high burden of morbidity and mortality. Globally, there is wide variation in the incidence of hip fracture in people aged 50 years and older. Longitudinal and cross-geographical comparisons of health data can provide insights on aetiology, risk factors, and healthcare practices. However, systematic reviews of studies that use different methods and study periods do not permit direct comparison across geographical regions. Thus, the objective of this study is to investigate global secular trends in hip fracture incidence, mortality and use of postfracture pharmacological treatment across Asia, Oceania, North and South America, and Western and Northern Europe using a unified methodology applied to health records. METHODS AND ANALYSIS: This retrospective cohort study will use a common protocol and an analytical common data model approach to examine incidence of hip fracture across population-based databases in different geographical regions and healthcare settings. The study period will be from 2005 to 2018 subject to data availability in study sites. Patients aged 50 years and older and hospitalised due to hip fracture during the study period will be included. The primary outcome will be expressed as the annual incidence of hip fracture. Secondary outcomes will be the pharmacological treatment rate and mortality within 12 months following initial hip fracture by year. For the primary outcome, crude and standardised incidence of hip fracture will be reported. Linear regression will be used to test for time trends in the annual incidence. For secondary outcomes, the crude mortality and standardised mortality incidence will be reported. ETHICS AND DISSEMINATION: Each participating site will follow the relevant local ethics and regulatory frameworks for study approval. The results of the study will be submitted for peer-reviewed scientific publications and presented at scientific conferences